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Operative Dentistry, 2007, 32-6, 549-555

In Vivo Study ofTwo Carbamide Peroxide Gels with DifferentDesensitizing Agents

BA Matis MA Cochran GJ Eckert JI Matis

Clinical RelevanceUnder the conditions of this study, 15% carbamide peroxide with potassium nitrate and fluoride exhibited greater bleaching potential but exhibited no difference in sensitivity compared to 16% carbamide peroxide with amorphous calcium phosphate.

SUMMARYThis study evaluated tooth whitening and sensi- tivity that occurred during and after 14 days of overnight bleaching with 15% carbamide perox- ide gel with potassium nitrate and fluoride (Opalescence 15% PF, OP) and 16% carbamide peroxide with amorphous calcium phosphate (Nite White 16%, NW). Thirty-two subjects

*Bruce A Matis, DDS, MSD, professor and director of Clinical Research Section, Indiana University School of Dentistry, Indianapolis, IN, USAMichael A Cochran, DDS, MSD, professor and director of Graduate Operative Program, Indiana University School of Dentistry, Indianapolis, IN, USAGeorge J Eckert, MAS, Biostatistics Division, Indiana University School of Medicine, Indianapolis, IN, USAJeremy I Matis, BA, dental student, Indiana University School of Dentistry, Indianapolis, IN, USA*Reprint request: 1121 West Michigan Street, Indianapolis, IN 46202, USA; e-mail: bmatis@iupui.eduDOI: 10.2341/07-10

bleached their teeth using custom trays. The sub- jects had a baseline evaluation and returned after 7, 14, 21, 35 and 90 days for subjective and objective color evaluations. The subjects also recorded daily tooth and gingival sensitivity. The treatments were compared for differences in mean L*, a*, b* and shade guide rank order at baseline and each appointment thereafter, using repeated measures analysis of variance (ANOVA). OP and NW showed significant tooth whitening. Subjects using OP were significantly lighter in b* and E* than those using NW, while exhibiting no difference in tooth or gingival sensitivity overall or during any evaluation.INTRODUCTIONWhite teeth are believed to be associated with health and beauty; lighter colored teeth have become desir- able. Vital tooth whitening, the most conservative treat- ment for discolored teeth, can be performed with a high rate of success and less expense to the patient than restorative treatments, such as porcelain veneers, crowns or composite bonding.1

550Operative Dentistry

Matis & Others: In Vivo Study of Carbamide Peroxide with Two Different Desensitizing Agents551

At-home vital tooth bleaching has become common- place in dentistry.2-5 The main types of bleaching agents currently used are hydrogen and carbamide peroxide and are used in a variety of concentrations. Dental tis- sue sensitivity during bleaching is a common side effect6-8 and varies from patient to patient. Usually, the sensitivity is reversible and resolves itself over time or with the help of a desensitizing agent.9As the popularity of tooth bleaching has increased, improvements have been made to bleaching products. Currently, many different compounds have been added to tooth whitening gels to improve them. Of these newer agents, potassium nitrate10 and amorphous cal- cium phosphate (ACP)11 have been identified as agents that are thought to decrease sensitivity. It is believed that potassium nitrate reduces dental sensitivity by decreasing the ability of nerve fibers in the dental pulp to re-polarize after an initial depolarization due to pain sensation. Fluoride is added to potassium nitrate, because it is believed that fluoride aids in the reduction of sensitivity by blocking the dentin tubules, thus reducing fluid flow to the pulp chamber.10 It is also believed that ACP reduces sensitivity by blocking tubules and surface defects with hydroxyapatite crys- tals that form from the interaction of ACP and carbon- ate.11 There are limited studies comparing how or if the addition of these agents affects the tooth whitening potential of whitening gels.This study evaluated the amount of tooth whitening and sensitivity that occurred during and after 14 days of overnight bleaching with 15% carbamide peroxide gel with potassium nitrate and fluoride and 16% car- bamide peroxide gel with amorphous calcium phos- phate. The amount of rebound that occurred up to three months post-bleaching was also measured. This study utilized a split-mouth design, the effectiveness of which has been described in other studies.12-18 The null hypotheses are that there will be no difference between either bleaching product with regard to 1) lightening of the teeth, 2) color rebound or 3) tooth/gingival sensitiv- ity.METHODS AND MATERIALSThe materials used in this study were Opalescence 15% carbamide peroxide gel with potassium nitrate and flu- oride (OP) (Ultradent Products, Inc, South Jordan, UT, USA) and Nite White 16% carbamide peroxide with amorphous calcium phosphate (NW) (Discus Dental Inc, Culver City, CA, USA).This study received approval from the Indiana University Purdue University Indianapolis Institutional Review Board. Thirty-two subjects, 16 female and 16 male with a mean age of 57 years, were recruited through advertisements and met the Inclusion/Exclusion criteria.

The inclusion criteria required that the patient have all six maxillary anterior teeth, have no maxillary ante- rior teeth with more than 1/6 of the labial surface of their natural tooth covered with a restoration, be will- ing to sign a consent form, be at least 18 years of age, be able to return for periodic examinations, be willing to refrain from the use of tobacco products during the study period and have maxillary anterior teeth that are shade B54 or darker on the Trubyte Bioform Color Ordered Shade Guide (Dentsply/Trubyte, York, PA, USA).The exclusion criteria included a history of any med- ical disease that could interfere with the study or require special considerations, any use of tobacco prod- ucts within the past 30 days, any current or previous use of professionally applied or prescribed in-office or at-home bleaching agents, gross pathology in the oral cavity (excluding caries), a gingival index score greater than 1.0, any pregnant or lactating women or tetracy- cline-stained teeth.Each participant received, read and signed a consent form. Additionally, the subjects received a complete oral prophylaxis with a dental prophylaxis paste containing fluoride, which was used to remove extrinsic stain from the teeth in a period no greater than two months but no less than two weeks prior to the start of the study. A maxillary arch impression was taken with Jeltrate Plus (Dentsply LD Caulk Division, Milford, DE, USA) from which a study model was made from Microstone (Whip Mix Corp, Louisville, KY, USA).Prior to the baseline evaluations and tray manufac- ture, the products were randomly assigned to different halves of the subjects maxillary arch. This was accom- plished before the baseline evaluation, because the manufacturers instructions state that reservoirs are required for OP but are not needed for NW. The prod- ucts were used in custom trays, which were trimmed just shy of the gingival margins.At the baseline appointment, the surrounding tissues were visually examined for gingival health using the Loe-Silness Gingival Index.19 The color evaluations were performed by subjective shade guide matching of the maxillary anterior teeth using the Trubyte Bioform Color Ordered Shade Guide (Dentsply/Trubyte) arranged by value order and by using a colorimeter (Chroma Meter CR-321, Minolta, Osaka, Japan). Clinical photographs were also taken with a digital camera (Nikon S2Pro, Tokyo, Japan). The subjects were then required to return at 7, 14, 21, 35 and 90 days after baseline for subjective and objective color evalua- tions. The same procedures were repeated at each sub- sequent appointment. The evaluations were conducted in the same geographic location and under color cor- rected overhead lighting, with the same examiner per-

forming all of the evaluations. The evaluator was blind as to the product used.The colorimeter used a color system that was defined by the International Commission on Illumination in 1967 and is referred to as CIELAB.20 The color system is based on the following values: L*, which represents the value (lightness or darkness); a*, which represents the measurement along the red-green axis and b*, which represents the measurement along the yellow- blue axis. Total color differences or distances between two colors (E*) were calculated using the formula: E*=[(L*)2 + (a*)2 + (b*)2]1/2.18 For a darker tooth color that was not present on the Trubyte shade guide, color tab B90 was recorded when the color of the tooth was darker than the darkest shade tab, B85. There were only two cuspids that were darker than the dark- est available shade tab.

Table 1: Mean Change and SD of L*for All Time PeriodsDayOPMeanSDNWMeanSDp valueDelta0.000.000.000.00---L*076.282.765.072.360.0001147.053.085.992.950.0017215.042.543.762.550.0002352.381.231.961.420.0136902.081.131.841.070.0577 - indicates statistical significance - indicates marginally significantThe treatments were compared for differences in mean L*, a*, b* and shade guide rank order at baseline and at each return visit, using repeated measures analysis of variance (ANOVA). Terms included in the ANOVA were treatment, tooth type and the treatment- by-tooth type interaction. The repeated subject effect was used to model correlations between teeth. Change in colorimeter measurements and shade guide assess- ments were computed by subtracting the baseline measurements from the follow-up measurements. The treatments were compared for differences in mean L*, a*, b*, E* and shade guide rank order using repeated measures ANOVA. Termsincluded were for treatment, tooth type, time and all interactions in-between the three factors. Baseline measurements were included as covariates. The repeat- ed subject effect was used to model cor- relations between teeth and correlations over time.

Table 2: Mean Change and SD of a* for All Time PeriodsDayOPMeanSDNWMeanSDp valueDelta0.000.000.000.00---a*07-0.780.57-0.590.580.000114-1.220.56-1.060.540.001221-0.970.55-0.760.580.000135-0.760.56-0.690.610.084690-0.710.50-0.680.500.4196 - indicates statistical significanceThe subjects were asked to brush their teeth at least twice a day with a non- whitening toothpaste (Crest Cavity Protection, Procter & Gamble, Cincinnati, OH, USA) to standardize oral hygiene. They were also given a sheet on which to record daily any tooth and/or gum sensitivity on their right or left side using a five-point scale where: 1= none, 2 = mild, 3 = moderate, 4 = con- siderable and 5 = severe. Subjects who experienced more than a moderate degree of sensitivity on either side of their mouth were asked to return to the dental school to receive potassium nitrate desensitizing gel. The sheets containing the daily recordings were returned to the examiner at the two- week evaluation.

The treatments were compared for differences in daily gum and tooth sensitivity assessments using ANOVA, with terms for treatment, day and the treatment-by- day interaction and random subject effects to correlate the sensitivity values within and between days.RESULTSColor ChangesThe baseline mean measurements for the OP group were: L*=49.19, a*= -.053, b*=4.18 and shade guide value=20. The baseline mean measurements for the NW group were: L*=49.08, a*= -0.55, b*=4.14 and shade guide value=20. There were no significant differ- ences between the two groups for any of the baseline measurements.The data for L*, a*, b*, E* and shade guide value mean and standard deviation at all time meas- urements are displayed in Tables 1 through 5 and are graphically represented in Figures 1 through 5.OP had a significantly higher L* than NW at days 7, 14, 21 and 35 and was marginally higher at 90 days. OP had a significantly higher a* than NW at days 7, 14 and 21 and was marginally higher at week 35. OP had a signifi- cantly higher b* than NW at days 7, 14, 21, 35 and 90. OP had a significantly higher E* than NW at days 7, 14, 21, 35 and 90. OP had a significantly higher shade guide value than NW at days 7, 14 and 21. Significant color change was still occurring between day 35 and 90

for both products. Both groups had significant mean changes from the baseline to 14 days post-bleaching for L*, a*, b*, E* and shade guide values.

SensitivityTooth sensitivity comparisons were only possible through day 17 due to a lack of significant sensitivity after day 17. OP and NW were not significantly differ- ent overall (p=0.9773) or at any day

Table 3: Mean Change and SD of b* for All Time PeriodsDayOPMeanSDNWMeanSDp valueDelta0.000.000.000.00---b*07-4.751.48-3.641.460.000114-5.841.58-4.761.610.000121-4.771.55-3.601.580.000135-3.511.08-2.841.220.000190-3.180.79-2.671.000.0001 - indicates statistical significance(Figure 6). Additionally, gingival sensi- tivity comparisons were only possible through day 14 due to a lack of signifi- cant sensitivity after day 14. OP and NW were not significantly different overall (p=0.3321) or on any particular day (Table 6, Figure 6).DISCUSSION

Table 4: Mean Change and SD of E* for All Time PeriodsDayOPMeanSDNWMeanSDp valueDelta0.000.000.000.00---E*078.102.806.492.450.0001149.572.718.042.820.0001217.242.695.562.720.0001354.531.373.841.480.0002904.081.023.611.060.0001 - indicates statistical significanceDental bleaching has become popular because it is an easy, inexpensive way to improve a patients smile. Many effec- tive bleaching products can be found on the current market. However, as one of the side effects of bleaching is sensitivi- ty, manufacturers have started to add desensitizing agents to bleaching prod- ucts, two of which include potassium nitrate and amorphous calcium phos- phate (ACP). There is little prior research comparing the effectiveness of bleaching and the reduction of sensitiv- ity between products with desensitizing agents. However, other comparisons have been made that are clinically rele- vant.

Table 5: Mean Change and SD of Shade Guide Value at All Time PeriodsDayOPMeanSDNWMeanSDp valueDelta00.000.000.000.00---shadeguide7-12.193.66-11.053.630.001014-16.083.80-15.213.840.001021-14.333.84-13.773.800.027935-13.033.80-12.833.820.418690-12.303.79-12.183.810.6876 - indicates statistical significanceTam21 compared 10% carbamide per- oxide (CP) and 10% CP with potassium nitrate and fluoride (PF). A split-mouth study design was used on 21 subjects to determine the whitening ability and sensitivity from those two agents. Tam concluded that the addition of PF made no difference in the whitening ability of 10% CP but noted that it significantly reduced the amount of sensitivity.21 A study conducted by Giniger and others22 compared the differences between a 16% CP product and a 16% CP product with ACP added. These authors deter- mined that the addition of ACP caused

Table 6: Mean Change and SD of Gingival and Tooth Sensitivity Scores at 5, 10, 15 and 20 DaysGingival SensitivityTooth SensitivityOPNWOPNWDayMeanSDMeanSDMeanSDMeanSD51.160.511.160.451.340.651.340.55101.280.731.220.491.340.651.340.60151.000.001.000.001.220.491.160.37201.000.001.000.001.000.001.000.00a statistically signifi- cant decrease in sensi- tivity and a statistical- ly significant increase in whitening ability.22In addition to whitening ability and sensitivity, bleaching agents can also be

Figure 1: Change in mean L* scores.Figure 2: Change in mean a* scores.

Figure 3: Change in mean b* scores.Figure 4: Change in mean E* scores.

Figure 5: Change in mean shade guide values.Figure 6: Change in mean tooth and gingival scores.

compared using the microhardness of enamel. Although hardness was not measured in this study, this method of assessment can be used to determine the similarity of the products. In a recent study, it was determined that the use of 20% CP with PF eight hours a day for 42 days actually increased the microhardness of enamel as compared to baseline values.23 Cimilli and

Pameijer found no significant differences in the hard- ness values of teeth treated six hours a day for five days with 15% and 16% CP without any desensitizing agents.24The colorimeter measured color based on CIELAB values. It has been determined that successful dental bleaching will induce a positive change in L* (an

increase in value or lightness), a negative change in a* (a decrease in chroma or intensity of red) and a negative change in b* (a decrease in chroma or the intensity of yellow).6 The current study found results that met these color shifts (Figures 1 through 3). Color evaluation also occurred with the Trubyte Bioform Color Ordered Shade Guide (Dentsply/Trubyte). This guide is organized with higher value (lighter) tabs on the lower end of the scale and lower value (darker) tabs on the higher end of the scale.The current study compared 15% CP and PF (OP) with 16% CP with ACP (NW), which had not been accomplished previously. This study demonstrated that the reduction in sensitivity was similar between OP and NW. However, it was demonstrated that OP had a statistically significant improvement in some lightened areas over NW. It must be noted that this study did not take into account the other differences in composition of the bleaching agents, which might have had an effect. Additionally, the addition of fluoride in OP was not addressed. It has been theorized that fluoride improves the whitening effect and effectiveness of bleaching agents.23 Further research should be conducted to deter- mine if this same effect is exhibited with differing con- centrations of CP or if there is a difference if the bleach- ing agent used is hydrogen peroxide.CONCLUSIONS Both OP and NW demonstrated significant tooth whitening at the end of 14 days of bleaching and at the end of the three-month study. Subjects using OP were significantly lighter in tooth whitening than those who used NW in b* and E* overall and at each visit. Subjects using OP were significantly lighter in tooth whitening than those who used NW in L*, a* and shade guide overall at some follow-up vis- its. OP and NW were not different in tooth or gingi- val sensitivity overall or at any visit.

AcknowledgementsThis study was sponsored by Ultradent Products, Inc.

(Received 12 January 2007)References1. Barghi N (1998) Making a clinical decision for vital tooth bleaching: At-home or in-office? Compendium 19(8) 831-838.2. Faunce F (1983) Management of discolored teeth Dental Clinics of North America 27(4) 657-670.3. Jordan RE & Boksman L (1984) Conservative vital bleaching treatment of discolored dentition The Compendium of Continuing Education in Dentistry 5(10) 803-808.4. Goldstein RE (1987) Bleaching teeth: New materials-new role Journal of the American Dental Association 115(Special Issue) 44E-52E.5. Nathanson D & Parra C (1987) Bleaching vital teeth: A review and clinical study The Compendium of Continuing Education in Dentistry 8(7) 490-498.6. Matis BA, Cochran MA, Eckert G & Carlson TJ (1998) The efficacy and safety of a 10% carbamide peroxide bleaching gel Quintessence International 29(9) 555-563.7. Leonard R, Haywood VB & Phillips C (1997) Risk factors for developing tooth sensitivity and gingival irritation associated with nightguard vital bleaching Quintessence International 28(8) 527-534.8. Nathanson D (1997) Vital tooth bleaching; sensitivity and pulpal considerations Journal of the American Dental Association 128 41S-44S.9. Frysh H (1995) Chemistry of bleaching In: Goldstein RE, Garber DA (eds) Complete Dental Bleaching Quintessence Chicago.10. Haywood VB, Caughman F, Frazier KB & Myers ML (2001) Tray delivery of potassium nitrate-fluoride to reduce bleach- ing sensitivity Quintessence International 32(2) 105-109.11. Giniger M, Macdonald J, Ziemba S & Felix H (2005) The clin- ical performance of professionally dispensed bleaching gel with added amorphous calcium phosphate Journal of the American Dental Association 136(3) 383-392.12. Gonzalez-Ochoa J (2002) Histological changes to dental pulp after vital bleaching with 10% carbamide peroxide Masters Thesis Indiana University, Indianapolis, Indiana.13. Martin JH, Bishop JG, Guentherman RH & Dorman HL (1968) Cellular response of gingiva to prolonged application of dilute hydrogen peroxide Journal of Periodontology 39(4) 208-210.14. Mousa HN (1998) A clinical evaluation of bleaching agents of different concentrations Masters Thesis Indiana University, Indianapolis, Indiana.15. Panich M (1999) In vivo evaluation of 15-percent carbamide peroxide and 5.5-percent hydrogen peroxide whitening agents during daytime use Masters Thesis Indiana University, Indianapolis, Indiana.16. Mokhlis GR (1999) A three-month clinical evaluation of 20- percent carbamide peroxide and 7.5% hydrogen peroxide whitening agents during daytime use Masters Thesis Indiana University, Indianapolis, Indiana.17. Zekonis R (2002) Clinical evaluation of in-office and at-home bleaching treatments Masters Thesis Indiana University, Indianapolis, Indiana.18. Al-Shethri SE (2002) A clinical evaluation of two in-office bleaching products Masters Thesis Indiana University, Indianapolis, Indiana.19. Loee H & Silness J (1963) Periodontal disease in pregnancy: Prevalence and severity Acta Odontologica Scandinavica 21 533-551.20. International Commission on Illumination (1978) Recommendations on uniform color spaces, color difference equations, psychometric color terms Supplement 2 to CIE, publication 15 Paris: Bureau Central de la CIE.

21. Tam L (2001) Effect of potassium nitrate and fluoride on car- bamide peroxide bleaching Quintessence International 32(10) 766-770.22. Giniger M, MacDonald J, Spaid M & Felix H (2005) A 180- day clinical investigation of the tooth whitening efficacy of a bleaching gel with added amorphous calcium phosphate Journal of Clinical Dentistry 16(1) 11-16.23. Basting RT, Rodrigues AL & Serra MC (2003) The effects of seven carbamide peroxide bleaching agents on enamel micro- hardness over time Journal of the American Dental Association 134(10) 1335-1342.24. Cimilli H & Pameijer CH (2001) Effect of carbamide peroxide bleaching agents on the physical properties and chemical composition of enamel American Journal of Dentistry 14(2) 63-33.